The "area tempestas" (AT) is an epileptogenic trigger site within the deep prepiriform cortex. Both episodic and sustained (status epilepticus) convulsive seizures are elicited from AT, in response to the focal application of a variety of excitatory amino acid agonists, including glutamate, aspartate, kainate, NMDA and AMPA. These AT-evoked limbic motor seizures are distinct from tonic seizures evoked from the brainstem and have been proposed as a model of human complex partial seizures. It is well documented that sustained seizures induce neuronal damage in the brain. Therefore in this proposal, cupric-silver degeneration and Nissl staining techniques will be used to map the anatomical and functional substrates of neuronal damage associated with seizures evoked from the AT. First, the pattern of neuronal degeneration accompanying AT-evoked seizures will be examined. Next, major connections of a key anatomical structure will be disrupted in order to define the channel responsible for the spread of seizures contralateral to the injection side and hence neuronal damage. Subsequently, the circuitry and receptor mechanisms mediating seizure-related damage vis-a-vis different excitatory and inhibitory mechanisms will be investigated. In addition, by inhibiting certain key AT targets, profiles of neuronal damage induced by AT-evoked status epilepticus will be assessed. These studies are expected to provide us with an understanding of: (1) the neuronal circuitry involved in generating convulsive seizures triggered from this seminal epileptogenic site; (2) the role of these seizures in neuronal death; (3) the neurotransmitter receptor mechanisms mediating this neuronal damage; and (4) the role of AT targets in neuronal degeneration.